The reporter recently learned from the Guangdong Provincial Institute of Lung Cancer of Guangdong Provincial People's Hospital that the ALINA study led by Professor Wu Yilong was published online in the top international medical journal "New England Journal of Medicine" (IF=158.5) on April 11. The study revealed that the postoperative adjuvant treatment of early ALK-positive lung cancer, the choice of alectinib (ALK inhibitor) compared with standard chemotherapy, reduced the risk of recurrence, metastasis or death by 76%, and could effectively prevent and reduce the occurrence of brain metastases, and oral medication was safe and convenient, bringing tangible survival benefits to patients.
Expert team of Guangdong Provincial Institute of Lung Cancer.
In the past decade, genotyping-based molecular targeted therapy has revolutionized the treatment of patients with advanced non-small cell lung cancer, making it possible for advanced lung cancer to become a chronic disease. For patients with operable lung cancer, perioperative treatment, especially postoperative adjuvant therapy, is an important means to prevent recurrence and achieve disease cure. This study is another major breakthrough in the field of adjuvant targeted therapy for operable lung cancer, and contributes Chinese wisdom to the optimization of adjuvant therapy strategies for lung cancer worldwide.
Non-small cell lung cancer is the most common type of lung cancer, accounting for 80% to 85% of lung cancer patients. With the advancement of precision medicine, lung cancer patients with gene mutations such as EGFR, ALK, ROS1, and HER2 can significantly prolong their survival after treatment with targeted drugs.
Professor Zhong Wenzhao, director of the Guangdong Institute of Lung Cancer, said that ALK fusion variant lung cancer accounts for only 3%-5% of all lung cancers, and is difficult to detect early, also known as diamond mutations. It is characterized by a relatively young age of onset, concentrated in young adults, 10 years younger than the median age of general lung cancer, and non-smoking or light smoking. The pathological type is mostly adenocarcinoma, with a high degree of malignancy, which will develop into an advanced stage in a short time, and patients are often diagnosed with large lesions, lymph node metastasis, and poor survival prognosis.
Professor Zhong Wenzhao.
In addition, this type of lung cancer is prone to brain metastases and atypical imaging. Once brain metastases occur, the patient's quality of life decreases dramatically. Despite the low percentage, 75,000-89,000 people worldwide are diagnosed with ALK-positive lung cancer every year because of the large base of lung cancer. How to improve the perioperative survival rate of such lung cancer patients is an international problem.
At present, the main treatment for stage I-IIIA non-small cell lung cancer is surgical resection, but 21%-55% of patients still have recurrence and metastasis after complete resection. Postoperative adjuvant chemotherapy, as the previous standard regimen, improved survival by only 5%, and the adverse effects were obvious. However, due to the lack of clinical research data in this area, chemotherapy is still recommended by official guidelines as the standard treatment for ALK-positive non-small cell lung cancer after surgery.
In this regard, Professor Wu Yilong from the Guangdong Provincial Institute of Lung Cancer of Guangdong Provincial People's Hospital and Professor Ben Solomon from Peter McCarran Cancer Center in Australia jointly initiated the ALINA study in August 2018 in collaboration with 113 medical centers in 26 countries/regions around the world, comparing the efficacy and safety of adjuvant alectinib compared with adjuvant chemotherapy for stage IB (≥4cm)-IIIA non-small cell lung cancer that underwent complete resection and was confirmed to be ALK fusion-positive.
Professor Wu Yilong.
As of December 2021, a total of 257 patients were enrolled in the study, randomized 1:1, of whom 130 received 2 years of alectinib and 127 received 4 cycles of chemotherapy, with the primary endpoint being disease-free survival. After a median follow-up of 27.8 months, 14 (12 percent) of the 231 patients with stage II-IIIA disease developed recurrence or metastasis or death in the alectinib group and 45 (39 percent) in the chemotherapy group. The 2-year recurrence-free rates were 93.8% and 63.0%, respectively, while the 3-year recurrence-free rates were 88.3% and 53.3%, respectively. Compared with chemotherapy, alectinib reduced the risk of recurrence, metastasis or death by 76% and reduced the risk of brain metastases or death by 78%.
In addition, the design mode of chemotherapy removal in the study protocol allows patients to avoid the adverse reactions and fears caused by chemotherapy, suggesting that ALK-targeted drugs are safe and well tolerated, and are suitable for long-term oral administration as adjuvant therapy.
It is reported that the ALINA study is the first phase III randomized clinical trial in the world to confirm the efficacy of ALK inhibitors in the adjuvant targeted therapy of ALK-positive non-small cell lung cancer in the early stage. Since 2009, as the global leading PI of international multi-center clinical trials, Professor Wu Yilong has led a number of international multi-center clinical trials, and has been listed in the New England Journal of Medicine five times, among which the IPASS study and the AURA3 study established a new standard for targeted therapy for advanced lung cancer as a first-line and second-line treatment, and the ADAURA study established a new standard for postoperative adjuvant therapy for early lung cancer, which has rewritten the international guidelines for the diagnosis and treatment of lung cancer and the global clinical practice of lung cancer.
Previously, the IPASS study established gefitinib as a first-line treatment for EGFR-mutant lung cancer in a large-scale randomized controlled study for the first time. The AURA3 study demonstrated that osimertinib was superior to standard chemotherapy in patients with advanced non-small cell lung cancer (including head metastases) with T790M mutations who have progressed on first-line EGFR inhibitor therapy. The ADAURA study confirmed that adjuvant osimertinib for 3 years in operable EGFR mutation-positive patients increased the 5-year survival rate to 88% and reduced the risk of death by 51%.
Professor Zhong Wenzhao said that ALK-positive lung cancer is a highly malignant tumor, which requires the integration of internal medicine, surgery, radiotherapy and other disciplines, and the application of ALK inhibitors from one to three generations can greatly prolong the survival of advanced ALK lung cancer. At present, research on other targets for adjuvant targeted therapy for operable lung cancer is also in progress, and with the deepening of research, it will bring low-toxicity and efficient treatment mode and survival benefits to more lung cancer patients.
【Reporter】Jiang Ling
Correspondents: Hao Li, Zhang Lanxi
Source: Southern Rural Daily